Lung cancer, the most significant cause of cancer deaths in the US, is an urgent public health threat. It disproportionately affects populations that are already plagued by high poverty rates and low education levels. These populations experience both health disparities in the early diagnosis and treatment of cancer and are historically difficult to reach with cancer screening initiatives. While the results from the National Lung Screening Trial (NLST) indicated that low dose CT (LDCT) is an efficacious and cost-effective strategy for lung cancer screening (LCS), many uncertainties exist with respect to how patient, provider, health system, and societal factors may impact the quality, compliance, effectiveness, and the risk of harms associated with lung cancer screening, within community-based health systems who serve diverse populations. Spanning from Pennsylvania to Hawaii and including five heterogeneous health systems with diverse populations, our proposed PROSPR Research Center, the Center for Research to Optimize Precision Lung Cancer Screening (CPLS), brings together a team of experienced, interdisciplinary researchers and clinicians with long-standing collaborative ties that is well-positioned to pursue research related to the barriers and opportunities associated with the implementation of LCS programs within community settings. The health systems within CPLS include: Henry Ford Health System in Metro Detroit, Kaiser Permanente Colorado, Kaiser Permanente Hawaii, Marshfield Clinic Health System in rural Wisconsin, and University of Pennsylvania Health System. The ultimate goal of CPLS is to identify critical gaps in the LCS process and to design innovative multilevel interventions to reduce lung cancer mortality, particularly among underserved populations. To achieve this goal, CPLS will complete the following specific aims: 1) build a comprehensive data ecosystem by pooling and linking common data elements to capture the entire LCS process and to assess the patient, provider, facility, health system, and societal factors that affect LCS; 2) leverage the CPLS data resource to conduct four high- impact, observational studies of the multilevel factors associated with the LCS process; 3) based on findings from Aims 1 and 2, develop and test interventions to address identifiable gaps in care that may lead to health disparities in LCS, 4) actively participate in Trans-PROSPR research initiatives and collaborate with external investigators via the use of publicly-available CPLS datasets. Our center focuses on the inclusion of diverse, underserved populations that are defined by multiple factors that may adversely impact access to, and utilization of, cancer screening. In response to both the Surgeon General?s strong emphasis on the need to reduce lung cancer mortality and the Cancer Moonshot Blue Ribbon Panel?s focus on reducing the disproportionately high cancer death rates in underserved populations, CPLS will serve as a model for high- impact, translational research to reduce disparities in cancer mortality.